27958-85-6Relevant academic research and scientific papers
Syntheses of piperidine and perhydroazepine derivatives, precursors of two selective antagonists of muscarinic M2 receptors: AF-DX 384 and its perhydroazepine isomer
Perrio-Huard, Cecile,Ducandas, Christophe,Lasne, Marie Claire,Moreau, Bernard
, p. 2925 - 2932 (2007/10/03)
Several routes to the synthesis of the polyamines 2a and 2b required for the preparation of the muscarinic antagonists AF-DX 384 1a and its perhydroazepine isomer 1b respectively have been developed and compared. Piperidine 2a has been obtained in 4 steps in 13-15% overall yield from 2-(chloromethyl)-pyridine 3. The perhydroazepine 2b has been prepared in 4 steps in 49% overall yield from 3-aminolactam 7. Transformations of piperidinemethanol 11 afford exclusively compound 2a (5 steps, 17-20% overall yield), via the N-tosylpiperidine 12, but lead to a 1:1 mixture of isomers 2a and 2b (4 steps, 15-20% overall yield for compounds 2a and 2b) via the N-(cyanomethyl)piperidine 15. Limitations to the ring enlargement of piperidine derivatives as a function of the heterocyclic nitrogen substituent are defined.
